Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
muscarinic receptor,, bronchodilators, Chronic obstructive pulmonary disease,
Brief summary
GSK233705 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for the treatment of chronic obstructive pulmonary disease. This is a randomised, double-blind, placebo-controlled, dose ascending, parallel group study to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of twice daily inhaled doses of GSK233705B for 7 days, in COPD subjects.
Interventions
DRUGGSK233705B
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Men or women who are between 40 and 75 years of age * Female subjects must be of non-childbearing * Subject diagnosed with COPD * Body Mass Index 18.0 - 32.0 kg/m2 (inclusive) * Subject is a smoker or an ex-smoker * Subject has post-bronchodilator (200µg salbutamol) FEV1 of = 40% to = 80% of predicted normal. * Subject has FEV1/FVC \< 0.7 post-bronchodilator (200µg salbutamol). * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Subject is available to complete all study measurements and procedures. * Subjects have a 24hour holter recording that is within normal limits and does not demonstrate any clinically important abnormality that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.
Exclusion criteria
* Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study. * The subject has a positive pre-study alcohol screen. * The subject has a positive pre-study drug screen. * History of alcohol/drug abuse or dependence within 12 months of the study: Abuse * The subject has a positive pregnancy test. * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening * Subject has tested positive for HIV * The subject has participated in a clinical trial and has received a drug or a new chemical entity within 60 days or 5 half-lives * Exposure to more than three new chemical entities (NCE) within 10 months prior to the first dosing day or one NCE within 3 months prior to the first dosing day. * The subject has donated a unit (400ml) of blood within 60 days of screening, or, intends to donate during the study. * The subject has a known allergy or hypersensitivity to ipratropium bromide, atropine and any of its derivatives or milk protein/lactose. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation * Subject has prostate hypertrophy or narrow angle glaucoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Up to Day 7 | Holter monitors were switched on immediately prior to dosing (up to 15mins pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. It was assessed on Day 1 and 7. |
| Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Up to Day 7 (0-4 hour) | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. |
| Number of Participants With Abnormal 12-lead ECG Findings | Up to Day 7 (24 hour post dose) | Single measurements were taken at all time points. The pre-dose values were classed as Baseline. Data for number of participants with normal, abnormal not clinically significant and abnormal clinically significant is presented. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. |
| Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | Up to Day 7 (0-4 hour) | Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. |
| Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | Up to Day 7 (0-4 hour) | Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. |
| Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | Up to Day 7 (24-hour post dose) | It was assessed on 1, 2, 4, 9, 12 and 24 hours on Days 1 and 7. Also on Day 7, it was measured on 0 hour (Baseline). At all time points 3 measurements were taken and formal statistical analysis was carried out on the derived maximum readings. Data for adjusted mean is presented as least square mean. |
| Number of Participants Who Used Rescue Medication | Up to Day 7 | Inhaled salbutamol was used as a rescue medication. Participants were required to keep a diary of their rescue medication (total number of salbutamol doses taken) over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Days 1, 2, 7 and 8. |
| Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Up to Day 7 | Clinical chemistry parameters included urea, potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, creatine kinase, chloride, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyltransferase (GGT), albumin, sodium, phosphorus inorganic, calcium, alkaline phosphatase (ALP) and total protein. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the potential clinical concern (PCI) is provided. |
| Number of Participants With Abnormalities in Hematology Data of Clinical Concern | Up to Day 7 | Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the PCI is provided. |
| Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Up to Day 7 (pre dose) | Urinalysis parameters included protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites and pH. Sediment microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for: WBC, RBC, hyaline casts, granular casts and cellular casts. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). |
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Up to follow-up (approximately 45 days) | An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. |
| Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Up to Day 7 (24 hours post-dose) | Blood pressure was measured subsequent to 12 lead electrocardiogram (ECG). Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. |
| Summary of Mean Heart Rate | Up to Day 7 (24 hour post dose) | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. |
| Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | Up to Day 7 (0-4 hour) | Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. |
| Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Up to Day 7 (0-4 hour) | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. |
| Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | Up to Day 7 (0-4 hour) | Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urine Concentrations of GSK233705 | Day 1 and 7 throughout 24 hours | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data is presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose. |
| Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning samples. |
| Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning sample as adjusted geometric mean. |
| Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples as adjusted geometric mean. |
| Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples. |
| Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Day 1 and 7 throughout 24 hours | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as AM dose and PM dose. 12 hour pharmacokinetic sampling was before evening dose. |
| Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 1 and 7 throughout 24 hours | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose. |
| Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) | Day 1 and 7 throughout 24 hours | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study. 12 hour pharmacokinetic sampling was before evening dose. |
| Plasma Concentrations of GSK233705 | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose | Blood samples were collected at indicated time points. 12 hour pharmacokinetic (PK) sampling was before evening dose. |
Countries
Netherlands
Participant flow
Recruitment details
From 29 March 2007 to 11 October 2007, total of 23 participants with chronic obstructive pulmonary disease (COPD) were randomized at four centres in the Netherlands. DISKUS™ is registered product of GlaxoSmithKline.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg. | 6 |
| GSK233705 50 µg Twice Daily Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. | 9 |
| GSK233705 100 µg Twice Daily Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. | 8 |
| Total | 23 |
Baseline characteristics
| Characteristic | Placebo | GSK233705 50 µg Twice Daily | GSK233705 100 µg Twice Daily | Total |
|---|---|---|---|---|
| Age, Continuous | 60.0 Years STANDARD_DEVIATION 11.15 | 66.4 Years STANDARD_DEVIATION 6.31 | 59.0 Years STANDARD_DEVIATION 7.27 | 62.2 Years STANDARD_DEVIATION 8.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 8 Participants | 23 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 5 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 4 / 6 | 4 / 9 | 4 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B)
Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Time frame: Up to Day 7 (0-4 hour)
Population: All subject population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcB, Day 1 | 406.29 Milliseconds |
| Placebo | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcB, Day 7 | 400.21 Milliseconds |
| Placebo | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcF, Day 1 | 402.97 Milliseconds |
| Placebo | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcF, Day 7 | 395.77 Milliseconds |
| GSK233705 50 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcF, Day 7 | 408.06 Milliseconds |
| GSK233705 50 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcB, Day 1 | 410.71 Milliseconds |
| GSK233705 50 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcF, Day 1 | 405.10 Milliseconds |
| GSK233705 50 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcB, Day 7 | 409.23 Milliseconds |
| GSK233705 100 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcF, Day 7 | 418.08 Milliseconds |
| GSK233705 100 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcB, Day 7 | 416.71 Milliseconds |
| GSK233705 100 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcF, Day 1 | 420.63 Milliseconds |
| GSK233705 100 µg Twice Daily | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | QTcB, Day 1 | 416.86 Milliseconds |
95% CI: [-12.66, 21.49]
95% CI: [-5.13, 23.17]
95% CI: [-7.24, 28.38]
95% CI: [1.74, 31.26]
95% CI: [-16.51, 20.78]
95% CI: [1.2, 23.38]
95% CI: [-1.53, 36.85]
95% CI: [10.9, 33.73]
Primary
Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Time frame: Up to Day 7 (0-4 hour)
Population: All subject population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Day 1 | 68.32 Beats per minute |
| Placebo | Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Day 7 | 69.30 Beats per minute |
| GSK233705 50 µg Twice Daily | Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Day 1 | 70.58 Beats per minute |
| GSK233705 50 µg Twice Daily | Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Day 7 | 71.92 Beats per minute |
| GSK233705 100 µg Twice Daily | Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Day 1 | 68.48 Beats per minute |
| GSK233705 100 µg Twice Daily | Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Day 7 | 63.86 Beats per minute |
95% CI: [-5.58, 10.1]
95% CI: [-5.3, 10.54]
95% CI: [-8.17, 8.48]
95% CI: [-13.86, 2.97]
Primary
Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose
Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Time frame: Up to Day 7 (0-4 hour)
Population: All subject population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 1 | 132.52 Millimeters of mercury |
| Placebo | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 7 | 86.14 Millimeters of mercury |
| Placebo | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 7 | 132.43 Millimeters of mercury |
| Placebo | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 1 | 81.21 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 7 | 79.50 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 1 | 131.56 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 7 | 128.33 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 1 | 81.80 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 7 | 127.67 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 7 | 75.33 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 1 | 82.19 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 1 | 138.73 Millimeters of mercury |
95% CI: [-12.68, 10.75]
95% CI: [-12.92, 4.72]
95% CI: [-5.78, 18.19]
95% CI: [-13.79, 4.27]
95% CI: [-3.89, 5.06]
95% CI: [-11.62, -1.65]
95% CI: [-3.73, 5.68]
95% CI: [-16.05, -5.57]
Primary
Number of Participants Who Used Rescue Medication
Inhaled salbutamol was used as a rescue medication. Participants were required to keep a diary of their rescue medication (total number of salbutamol doses taken) over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Days 1, 2, 7 and 8.
Time frame: Up to Day 7
Population: All subject population was used.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Used Rescue Medication | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants Who Used Rescue Medication | 4 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants Who Used Rescue Medication | 2 Participants |
Primary
Number of Participants With Abnormal 12-lead ECG Findings
Single measurements were taken at all time points. The pre-dose values were classed as Baseline. Data for number of participants with normal, abnormal not clinically significant and abnormal clinically significant is presented. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Time frame: Up to Day 7 (24 hour post dose)
Population: All subject population was used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Normal | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Normal | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Normal | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Normal | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Normal | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Abnormal not clinically significant | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Abnormal not clinically significant | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Abnormal not clinically significant | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Normal | 1 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Abnormal not clinically significant | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Abnormal not clinically significant | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Normal | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Abnormal not clinically significant | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Normal | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Abnormal not clinically significant | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Abnormal not clinically significant | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Normal | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Abnormal not clinically significant | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Abnormal not clinically significant | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Normal | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Abnormal not clinically significant | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Normal | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Abnormal not clinically significant | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Abnormal not clinically significant | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Normal | 3 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Normal | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Abnormal not clinically significant | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Normal | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Abnormal clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Abnormal not clinically significant | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Normal | 3 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Normal | 7 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Normal | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Abnormal not clinically significant | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Abnormal not clinically significant | 6 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Normal | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Abnormal not clinically significant | 6 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Normal | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Abnormal not clinically significant | 5 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Normal | 3 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Abnormal not clinically significant | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Abnormal not clinically significant | 2 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Normal | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Normal | 3 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Normal | 5 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Normal | 5 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Abnormal not clinically significant | 2 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Abnormal not clinically significant | 2 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Abnormal not clinically significant | 2 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Abnormal not clinically significant | 2 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 24 hour | Abnormal not clinically significant | 2 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Normal | 5 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 15 minutes | Abnormal not clinically significant | 3 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Normal | 5 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Abnormal not clinically significant | 3 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 30 minutes | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Abnormal not clinically significant | 5 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 1.5 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Normal | 5 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Abnormal not clinically significant | 3 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 4 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Abnormal not clinically significant | 3 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 8 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Abnormal not clinically significant | 3 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, 24 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, Baseline | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 15 minutes | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 30 minutes | Abnormal not clinically significant | 2 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 1.5 hour | Abnormal not clinically significant | 2 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 4 hour | Abnormal clinically significant | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 7, 8 hour | Normal | 6 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormal 12-lead ECG Findings | Day 1, Baseline | Abnormal not clinically significant | 2 Participants |
Primary
Number of Participants With Abnormalities in Chemistry Data of Clinical Concern
Clinical chemistry parameters included urea, potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, creatine kinase, chloride, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyltransferase (GGT), albumin, sodium, phosphorus inorganic, calcium, alkaline phosphatase (ALP) and total protein. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the potential clinical concern (PCI) is provided.
Time frame: Up to Day 7
Population: All subject population was used.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Inorganic phosphorus, Low | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Glucose, High | 0 Participants |
| Placebo | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Inorganic phosphorus, High | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Inorganic phosphorus, Low | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Glucose, High | 1 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Inorganic phosphorus, High | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Glucose, High | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Inorganic phosphorus, High | 1 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Inorganic phosphorus, Low | 1 Participants |
Primary
Number of Participants With Abnormalities in Hematology Data of Clinical Concern
Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the PCI is provided.
Time frame: Up to Day 7
Population: All subject population was used.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Abnormalities in Hematology Data of Clinical Concern | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Abnormalities in Hematology Data of Clinical Concern | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Abnormalities in Hematology Data of Clinical Concern | 0 Participants |
Primary
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Time frame: Up to follow-up (approximately 45 days)
Population: All subject population included all available data on participants who had received at least one dose of study medication (including placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 4 Participants |
| Placebo | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 0 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 4 Participants |
| GSK233705 50 µg Twice Daily | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 0 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AE | 4 Participants |
| GSK233705 100 µg Twice Daily | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAE | 0 Participants |
Primary
Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data
Holter monitors were switched on immediately prior to dosing (up to 15mins pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. It was assessed on Day 1 and 7.
Time frame: Up to Day 7
Population: All subject population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Maximum heart rate, Day 7 | 114.02 Beats per minute |
| Placebo | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Mean heart rate, Day 1 | 71.260 Beats per minute |
| Placebo | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Maximum heart rate, Day 1 | 113.35 Beats per minute |
| Placebo | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Mean heart rate, Day 7 | 68.670 Beats per minute |
| GSK233705 50 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Mean heart rate, Day 7 | 73.453 Beats per minute |
| GSK233705 50 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Maximum heart rate, Day 7 | 119.75 Beats per minute |
| GSK233705 50 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Maximum heart rate, Day 1 | 115.58 Beats per minute |
| GSK233705 50 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Mean heart rate, Day 1 | 73.994 Beats per minute |
| GSK233705 100 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Mean heart rate, Day 7 | 70.239 Beats per minute |
| GSK233705 100 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Mean heart rate, Day 1 | 70.186 Beats per minute |
| GSK233705 100 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Maximum heart rate, Day 1 | 112.08 Beats per minute |
| GSK233705 100 µg Twice Daily | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Maximum heart rate, Day 7 | 115.01 Beats per minute |
95% CI: [-4.743, 9.21]
95% CI: [-11.2, 22.664]
95% CI: [-8.051, 5.507]
95% CI: [-15.47, 17.443]
95% CI: [-4.468, 9.936]
95% CI: [-1.372, 10.938]
95% CI: [-8.003, 5.854]
95% CI: [-4.353, 7.49]
Primary
Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC)
It was assessed on 1, 2, 4, 9, 12 and 24 hours on Days 1 and 7. Also on Day 7, it was measured on 0 hour (Baseline). At all time points 3 measurements were taken and formal statistical analysis was carried out on the derived maximum readings. Data for adjusted mean is presented as least square mean.
Time frame: Up to Day 7 (24-hour post dose)
Population: All subject population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 4 hour | 1.604 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 9 hour | 3.449 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 4 hour | 1.687 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 12 hour | 3.544 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, Baseline | 1.515 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 24 hour | 3.449 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 2 hour | 1.665 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 24 hour | 1.644 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 1 hour | 1.713 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 9 hour | 3.571 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 9 hour | 1.614 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 2 hour | 1.726 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 9 hour | 1.598 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 12 hour | 3.316 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 4 hour | 3.596 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 24 hour | 1.614 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 4 hour | 3.465 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 2 hour | 3.689 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 24 hour | 3.593 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 12 hour | 1.616 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 1 hour | 3.623 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, Baseline | 3.266 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 1 hour | 3.375 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 12 hour | 1.526 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 2 hour | 3.503 Liters |
| Placebo | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 1 hour | 1.560 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 2 hour | 1.897 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 9 hour | 1.764 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 1 hour | 1.789 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 9 hour | 1.804 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 24 hour | 1.820 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 24 hour | 3.708 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 1 hour | 3.644 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 2 hour | 3.524 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 9 hour | 3.714 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 12 hour | 3.683 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 24 hour | 3.691 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 1 hour | 1.860 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 4 hour | 1.747 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 12 hour | 1.740 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 24 hour | 1.807 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, Baseline | 1.751 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 2 hour | 1.760 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 4 hour | 1.777 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 12 hour | 1.746 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 1 hour | 3.761 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 2 hour | 3.819 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 4 hour | 3.558 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 9 hour | 3.631 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 12 hour | 3.658 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, Baseline | 3.628 Liters |
| GSK233705 50 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 4 hour | 3.642 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 9 hour | 1.878 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 1 hour | 3.999 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 9 hour | 3.894 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 24 hour | 3.755 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, Baseline | 3.801 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 1 hour | 3.776 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 24 hour | 1.793 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, Baseline | 1.771 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 2 hour | 4.009 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 12 hour | 1.719 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 2 hour | 3.962 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 4 hour | 3.907 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 4 hour | 1.811 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 4 hour | 1.953 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 1 hour | 1.919 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 9 hour | 1.934 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 12 hour | 1.788 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 24 hour | 3.832 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 9 hour | 3.919 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 24 hour | 1.798 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 12 hour | 3.600 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 1 hour | 1.856 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 1, 2 hour | 2.055 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FEV1, Day 7, 2 hour | 1.867 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 7, 4 hour | 3.929 Liters |
| GSK233705 100 µg Twice Daily | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | FVC, Day 1, 12 hour | 3.789 Liters |
95% CI: [-0.035, 0.328]
95% CI: [-0.015, 0.357]
95% CI: [-0.107, 0.228]
95% CI: [-0.085, 0.386]
95% CI: [-0.094, 0.343]
95% CI: [-0.077, 0.404]
95% CI: [0.027, 0.444]
95% CI: [-0.026, 0.483]
95% CI: [-0.163, 0.353]
95% CI: [-0.072, 0.418]
95% CI: [-0.09, 0.501]
95% CI: [-0.062, 0.502]
95% CI: [-0.093, 0.506]
95% CI: [0.015, 0.397]
95% CI: [0.133, 0.525]
95% CI: [0.09, 0.443]
95% CI: [0.072, 0.568]
95% CI: [-0.058, 0.402]
95% CI: [-0.099, 0.407]
95% CI: [0.036, 0.475]
95% CI: [0.027, 0.564]
95% CI: [-0.069, 0.474]
95% CI: [-0.051, 0.465]
95% CI: [-0.032, 0.591]
95% CI: [-0.104, 0.49]
95% CI: [-0.136, 0.495]
95% CI: [-0.263, 0.537]
95% CI: [-0.257, 0.518]
95% CI: [-0.414, 0.338]
95% CI: [-0.337, 0.457]
95% CI: [-0.343, 0.572]
95% CI: [-0.277, 0.507]
95% CI: [-0.19, 0.914]
95% CI: [-0.263, 0.8]
95% CI: [-0.501, 0.543]
95% CI: [-0.337, 0.691]
95% CI: [-0.263, 0.795]
95% CI: [-0.209, 0.943]
95% CI: [-0.283, 0.768]
95% CI: [-0.263, 0.567]
95% CI: [-0.081, 0.723]
95% CI: [-0.079, 0.701]
95% CI: [-0.064, 0.76]
95% CI: [-0.23, 0.72]
95% CI: [-0.245, 0.569]
95% CI: [-0.038, 1.108]
95% CI: [0.072, 1.175]
95% CI: [-0.083, 1]
95% CI: [-0.069, 0.997]
95% CI: [-0.104, 0.994]
95% CI: [-0.314, 0.882]
95% CI: [-0.162, 0.929]
Primary
Summary of Mean Heart Rate
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Time frame: Up to Day 7 (24 hour post dose)
Population: All subject population was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Summary of Mean Heart Rate | Day 7, 24 hour | 68.0 Beats per minute | Standard Deviation 9.78 |
| Placebo | Summary of Mean Heart Rate | Day 7, 15 minutes | 65.3 Beats per minute | Standard Deviation 6.56 |
| Placebo | Summary of Mean Heart Rate | Day 1, 4 hour | 63.2 Beats per minute | Standard Deviation 6.31 |
| Placebo | Summary of Mean Heart Rate | Day 7, 4 hour | 64.3 Beats per minute | Standard Deviation 8.91 |
| Placebo | Summary of Mean Heart Rate | Day 7, Baseline | 63.6 Beats per minute | Standard Deviation 4.62 |
| Placebo | Summary of Mean Heart Rate | Day 1, 8 hour | 65.7 Beats per minute | Standard Deviation 5.75 |
| Placebo | Summary of Mean Heart Rate | Day 1, 15 minutes | 62.2 Beats per minute | Standard Deviation 8.06 |
| Placebo | Summary of Mean Heart Rate | Day 1, 24 hour | 62.3 Beats per minute | Standard Deviation 10.25 |
| Placebo | Summary of Mean Heart Rate | Day 7, 8 hour | 65.3 Beats per minute | Standard Deviation 4.89 |
| Placebo | Summary of Mean Heart Rate | Day 7, 1.5 hour | 60.0 Beats per minute | Standard Deviation 7.01 |
| Placebo | Summary of Mean Heart Rate | Day 1, 30 minutes | 61.2 Beats per minute | Standard Deviation 5.78 |
| Placebo | Summary of Mean Heart Rate | Day 1, Baseline | 65.7 Beats per minute | Standard Deviation 7.07 |
| Placebo | Summary of Mean Heart Rate | Day 7, 30 minutes | 63.3 Beats per minute | Standard Deviation 6.25 |
| Placebo | Summary of Mean Heart Rate | Day 1, 1.5 hour | 64.7 Beats per minute | Standard Deviation 9.52 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 7, Baseline | 67.0 Beats per minute | Standard Deviation 8.2 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 30 minutes | 66.7 Beats per minute | Standard Deviation 11.79 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 1, Baseline | 66.7 Beats per minute | Standard Deviation 9.68 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 15 minutes | 65.1 Beats per minute | Standard Deviation 8.07 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 30 minutes | 64.9 Beats per minute | Standard Deviation 8.57 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 1.5 hour | 62.7 Beats per minute | Standard Deviation 9.63 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 4 hour | 66.6 Beats per minute | Standard Deviation 14.57 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 8 hour | 68.1 Beats per minute | Standard Deviation 11.12 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 24 hour | 68.1 Beats per minute | Standard Deviation 13.13 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 24 hour | 70.2 Beats per minute | Standard Deviation 17.22 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 15 minutes | 68.3 Beats per minute | Standard Deviation 14.27 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 1.5 hour | 64.0 Beats per minute | Standard Deviation 11.61 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 4 hour | 66.2 Beats per minute | Standard Deviation 12.72 |
| GSK233705 50 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 8 hour | 66.1 Beats per minute | Standard Deviation 7.62 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 1.5 hour | 64.9 Beats per minute | Standard Deviation 6.29 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 30 minutes | 65.0 Beats per minute | Standard Deviation 7.33 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 15 minutes | 64.5 Beats per minute | Standard Deviation 6.55 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 30 minutes | 66.6 Beats per minute | Standard Deviation 7.42 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 15 minutes | 70.4 Beats per minute | Standard Deviation 10.57 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 24 hour | 65.5 Beats per minute | Standard Deviation 5.98 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 1.5 hour | 62.5 Beats per minute | Standard Deviation 8.25 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 1, Baseline | 71.5 Beats per minute | Standard Deviation 8.5 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 8 hour | 66.9 Beats per minute | Standard Deviation 6.01 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 8 hour | 66.3 Beats per minute | Standard Deviation 5.47 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 24 hour | 65.5 Beats per minute | Standard Deviation 8.45 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 1, 4 hour | 64.0 Beats per minute | Standard Deviation 8.37 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 7, 4 hour | 63.0 Beats per minute | Standard Deviation 8.43 |
| GSK233705 100 µg Twice Daily | Summary of Mean Heart Rate | Day 7, Baseline | 67.8 Beats per minute | Standard Deviation 8.3 |
Primary
Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure was measured subsequent to 12 lead electrocardiogram (ECG). Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7.
Time frame: Up to Day 7 (24 hours post-dose)
Population: All subject population was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 15 minutes | 130.0 Millimeters of mercury | Standard Deviation 12.84 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 8 hour | 75.3 Millimeters of mercury | Standard Deviation 9.16 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 1.5 hour | 127.0 Millimeters of mercury | Standard Deviation 16.12 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 24 hour | 78.8 Millimeters of mercury | Standard Deviation 9.39 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 4 hour | 77.3 Millimeters of mercury | Standard Deviation 9.42 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 4 hour | 127.2 Millimeters of mercury | Standard Deviation 13.26 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 1.5 hour | 131.2 Millimeters of mercury | Standard Deviation 16.17 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 1.5 hour | 74.8 Millimeters of mercury | Standard Deviation 6.82 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 8 hour | 131.0 Millimeters of mercury | Standard Deviation 20.71 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 30 minutes | 126.0 Millimeters of mercury | Standard Deviation 14.24 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 30 minutes | 76.2 Millimeters of mercury | Standard Deviation 8.8 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 24 hour | 130.3 Millimeters of mercury | Standard Deviation 15.96 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 8 hour | 79.0 Millimeters of mercury | Standard Deviation 12.66 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 15 minutes | 78.0 Millimeters of mercury | Standard Deviation 7.43 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, Baseline | 74.7 Millimeters of mercury | Standard Deviation 8.69 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 1.5 hour | 78.2 Millimeters of mercury | Standard Deviation 10.57 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 8 hour | 132.8 Millimeters of mercury | Standard Deviation 14.26 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 30 minutes | 78.8 Millimeters of mercury | Standard Deviation 10.7 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 24 hour | 131.5 Millimeters of mercury | Standard Deviation 13.49 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, Baseline | 129.2 Millimeters of mercury | Standard Deviation 15.37 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 15 minutes | 82.5 Millimeters of mercury | Standard Deviation 10.97 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, Baseline | 124.6 Millimeters of mercury | Standard Deviation 15.25 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 4 hour | 126.2 Millimeters of mercury | Standard Deviation 17.52 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, Baseline | 77.0 Millimeters of mercury | Standard Deviation 8.8 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 15 minutes | 127.5 Millimeters of mercury | Standard Deviation 16.43 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 4 hour | 79.3 Millimeters of mercury | Standard Deviation 7.69 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 24 hour | 77.2 Millimeters of mercury | Standard Deviation 6.05 |
| Placebo | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 30 minutes | 122.5 Millimeters of mercury | Standard Deviation 22.21 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 1.5 hour | 76.8 Millimeters of mercury | Standard Deviation 4.27 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 1.5 hour | 124.1 Millimeters of mercury | Standard Deviation 13.01 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 4 hour | 124.8 Millimeters of mercury | Standard Deviation 9.9 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, Baseline | 127.7 Millimeters of mercury | Standard Deviation 9.03 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 15 minutes | 130.0 Millimeters of mercury | Standard Deviation 8.99 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 30 minutes | 123.7 Millimeters of mercury | Standard Deviation 10.85 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 8 hour | 121.1 Millimeters of mercury | Standard Deviation 9.44 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 24 hour | 123.1 Millimeters of mercury | Standard Deviation 7.64 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, Baseline | 122.7 Millimeters of mercury | Standard Deviation 11.94 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 15 minutes | 123.1 Millimeters of mercury | Standard Deviation 12.75 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 30 minutes | 124.6 Millimeters of mercury | Standard Deviation 13.41 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 1.5 hour | 122.8 Millimeters of mercury | Standard Deviation 12.55 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 4 hour | 122.7 Millimeters of mercury | Standard Deviation 10.78 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 8 hour | 123.3 Millimeters of mercury | Standard Deviation 12.59 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 24 hour | 126.6 Millimeters of mercury | Standard Deviation 11.67 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, Baseline | 77.4 Millimeters of mercury | Standard Deviation 4.29 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 15 minutes | 78.9 Millimeters of mercury | Standard Deviation 4.11 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 30 minutes | 77.0 Millimeters of mercury | Standard Deviation 5 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 1.5 hour | 76.2 Millimeters of mercury | Standard Deviation 4.02 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 4 hour | 80.3 Millimeters of mercury | Standard Deviation 5.32 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 8 hour | 75.7 Millimeters of mercury | Standard Deviation 5.41 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 24 hour | 77.4 Millimeters of mercury | Standard Deviation 3.32 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, Baseline | 76.7 Millimeters of mercury | Standard Deviation 5.15 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 15 minutes | 76.1 Millimeters of mercury | Standard Deviation 4.65 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 30 minutes | 77.7 Millimeters of mercury | Standard Deviation 4.58 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 4 hour | 78.2 Millimeters of mercury | Standard Deviation 4.55 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 8 hour | 75.6 Millimeters of mercury | Standard Deviation 5.15 |
| GSK233705 50 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 24 hour | 77.4 Millimeters of mercury | Standard Deviation 4.61 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 4 hour | 77.9 Millimeters of mercury | Standard Deviation 12.08 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 30 minutes | 119.5 Millimeters of mercury | Standard Deviation 9.58 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 1.5 hour | 133.5 Millimeters of mercury | Standard Deviation 18.47 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 8 hour | 72.6 Millimeters of mercury | Standard Deviation 10.95 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 15 minutes | 123.6 Millimeters of mercury | Standard Deviation 11.13 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 4 hour | 74.0 Millimeters of mercury | Standard Deviation 12.72 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 24 hour | 76.0 Millimeters of mercury | Standard Deviation 12.98 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, Baseline | 123.9 Millimeters of mercury | Standard Deviation 9.21 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 4 hour | 132.1 Millimeters of mercury | Standard Deviation 12.96 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, Baseline | 75.4 Millimeters of mercury | Standard Deviation 7.21 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 24 hour | 129.6 Millimeters of mercury | Standard Deviation 16.1 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 24 hour | 73.4 Millimeters of mercury | Standard Deviation 11.5 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 15 minutes | 75.0 Millimeters of mercury | Standard Deviation 9.97 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 8 hour | 124.0 Millimeters of mercury | Standard Deviation 13.03 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 8 hour | 73.4 Millimeters of mercury | Standard Deviation 8.33 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 30 minutes | 74.9 Millimeters of mercury | Standard Deviation 11.13 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, Baseline | 80.0 Millimeters of mercury | Standard Deviation 10.6 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 24 hour | 129.1 Millimeters of mercury | Standard Deviation 10.64 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 30 minutes | 128.4 Millimeters of mercury | Standard Deviation 9.32 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 15 minutes | 81.1 Millimeters of mercury | Standard Deviation 9.95 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 8 hour | 123.1 Millimeters of mercury | Standard Deviation 13.22 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, 15 minutes | 130.6 Millimeters of mercury | Standard Deviation 16.04 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 30 minutes | 77.3 Millimeters of mercury | Standard Deviation 10.61 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 4 hour | 123.9 Millimeters of mercury | Standard Deviation 15.42 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 7, 1.5 hour | 73.6 Millimeters of mercury | Standard Deviation 8.99 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, Day 1, 1.5 hour | 78.4 Millimeters of mercury | Standard Deviation 8.35 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 7, 1.5 hour | 123.9 Millimeters of mercury | Standard Deviation 10.86 |
| GSK233705 100 µg Twice Daily | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, Day 1, Baseline | 129.6 Millimeters of mercury | Standard Deviation 11.78 |
Primary
Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results
Urinalysis parameters included protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites and pH. Sediment microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for: WBC, RBC, hyaline casts, granular casts and cellular casts. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours).
Time frame: Up to Day 7 (pre dose)
Population: All subject population was used.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-RBC-Day 1 | 1 Participants |
| Placebo | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-WBC-Day 1 | 0 Participants |
| Placebo | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-RBC-Day 7 | 1 Participants |
| Placebo | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-WBC-Day 7 | 1 Participants |
| GSK233705 50 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-RBC-Day 1 | 0 Participants |
| GSK233705 50 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-WBC-Day 7 | 1 Participants |
| GSK233705 50 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-RBC-Day 7 | 1 Participants |
| GSK233705 50 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-WBC-Day 1 | 0 Participants |
| GSK233705 100 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-WBC-Day 1 | 1 Participants |
| GSK233705 100 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-RBC-Day 1 | 0 Participants |
| GSK233705 100 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-RBC-Day 7 | 0 Participants |
| GSK233705 100 µg Twice Daily | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urine microscopy-WBC-Day 7 | 1 Participants |
Primary
Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B
Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Time frame: Up to Day 7 (0-4 hour)
Population: All subject population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcB, Day 1 | 393.77 Milliseconds |
| Placebo | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcB, Day 7 | 392.54 Milliseconds |
| Placebo | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcF, Day 1 | 391.25 Milliseconds |
| Placebo | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcF, Day 7 | 390.72 Milliseconds |
| GSK233705 50 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcF, Day 7 | 399.47 Milliseconds |
| GSK233705 50 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcB, Day 1 | 403.33 Milliseconds |
| GSK233705 50 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcF, Day 1 | 399.57 Milliseconds |
| GSK233705 50 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcB, Day 7 | 400.93 Milliseconds |
| GSK233705 100 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcF, Day 7 | 411.18 Milliseconds |
| GSK233705 100 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcB, Day 7 | 407.83 Milliseconds |
| GSK233705 100 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcF, Day 1 | 408.08 Milliseconds |
| GSK233705 100 µg Twice Daily | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | QTcB, Day 1 | 405.25 Milliseconds |
95% CI: [-1.46, 20.57]
95% CI: [-3.97, 20.74]
95% CI: [-0.02, 22.96]
95% CI: [2.39, 28.17]
95% CI: [-1.35, 18]
95% CI: [-2.21, 19.72]
95% CI: [6.87, 26.79]
95% CI: [9.17, 31.75]
Primary
Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose
Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Time frame: Up to Day 7 (0-4 hour)
Population: All subject population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Day 1 | 65.46 Beats per minute |
| Placebo | Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Day 7 | 64.31 Beats per minute |
| GSK233705 50 µg Twice Daily | Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Day 1 | 65.60 Beats per minute |
| GSK233705 50 µg Twice Daily | Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Day 7 | 66.70 Beats per minute |
| GSK233705 100 µg Twice Daily | Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Day 1 | 62.79 Beats per minute |
| GSK233705 100 µg Twice Daily | Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Day 7 | 60.47 Beats per minute |
95% CI: [-5.52, 5.79]
95% CI: [-3.5, 8.28]
95% CI: [-8.67, 3.34]
95% CI: [-10.1, 2.41]
Primary
Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose
Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean.
Time frame: Up to Day 7 (0-4 hour)
Population: All subject population was used.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 1 | 128.31 Millimeters of mercury |
| Placebo | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 7 | 125.87 Millimeters of mercury |
| Placebo | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 1 | 78.22 Millimeters of mercury |
| Placebo | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 7 | 81.37 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 7 | 77.49 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 1 | 125.53 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 1 | 77.94 Millimeters of mercury |
| GSK233705 50 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 7 | 123.99 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 7 | 71.99 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 7 | 122.37 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | DBP, Day 1 | 76.47 Millimeters of mercury |
| GSK233705 100 µg Twice Daily | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | SBP, Day 1 | 131.32 Millimeters of mercury |
95% CI: [-12.43, 6.87]
95% CI: [-10.07, 6.31]
95% CI: [-6.87, 12.88]
95% CI: [-11.88, 4.89]
95% CI: [-4.09, 3.54]
95% CI: [-8.32, 0.54]
95% CI: [-5.76, 2.26]
95% CI: [-14.04, -4.73]
Secondary
Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples as adjusted geometric mean.
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Population: PK population was used.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | AM Dose, Day 1 | 0.035 Nanograms per liter |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | PM Dose, Day 1 | 0.052 Nanograms per liter |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | AM Dose, Day 7 | 0.049 Nanograms per liter |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | PM Dose, Day 7 | 0.051 Nanograms per liter |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | AM Dose, Day 7 | 0.190 Nanograms per liter |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | AM Dose, Day 1 | 0.160 Nanograms per liter |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | PM Dose, Day 7 | 0.191 Nanograms per liter |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | PM Dose, Day 1 | 0.186 Nanograms per liter |
90% CI: [0.934, 2.122]
90% CI: [0.77, 1.838]
90% CI: [0.658, 1.457]
90% CI: [0.674, 1.568]
Secondary
Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples.
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Population: PK population was used.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-half, Day 1, AM dose | 0.624 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-half, Day 7, AM dose | 4.122 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 1, PM dose | 0.080 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 7, PM dose | 0.080 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 1, AM dose | 1.000 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 7, AM dose | 11.920 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 1, PM dose | 0.500 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 7, PM dose | 0.500 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 1, AM dose | 0.080 Hour |
| Placebo | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 7, AM dose | 0.230 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 7, PM dose | 0.500 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-half, Day 1, AM dose | 1.167 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 7, AM dose | 11.920 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 7, AM dose | 0.080 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 1, PM dose | 0.080 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 1, PM dose | 0.500 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 7, PM dose | 0.080 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-half, Day 7, AM dose | 7.189 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-max, Day 1, AM dose | 0.080 Hour |
| GSK233705 50 µg Twice Daily | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | T-last, Day 1, AM dose | 2.025 Hour |
Secondary
Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning sample as adjusted geometric mean.
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Population: PK population was used.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Placebo | Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Day 1 | 0.016 Hour×Nanograms per milliliter |
| Placebo | Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Day 7 | 0.018 Hour×Nanograms per milliliter |
| GSK233705 50 µg Twice Daily | Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Day 1 | 0.053 Hour×Nanograms per milliliter |
| GSK233705 50 µg Twice Daily | Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Day 7 | 0.056 Hour×Nanograms per milliliter |
90% CI: [0.811, 1.601]
90% CI: [0.739, 1.52]
Secondary
Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau)
Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning samples.
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Population: PK population was used.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) | Day 1 | 0.044 Hour×Nanograms per milliliter | Geometric Coefficient of Variation 28.2 |
| Placebo | Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) | Day 7 | 0.189 Hour×Nanograms per milliliter | Geometric Coefficient of Variation 39.3 |
| GSK233705 50 µg Twice Daily | Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) | Day 1 | 0.147 Hour×Nanograms per milliliter | Geometric Coefficient of Variation 43 |
| GSK233705 50 µg Twice Daily | Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) | Day 7 | 0.430 Hour×Nanograms per milliliter | Geometric Coefficient of Variation 44.5 |
Secondary
Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae)
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as AM dose and PM dose. 12 hour pharmacokinetic sampling was before evening dose.
Time frame: Day 1 and 7 throughout 24 hours
Population: PK population was used.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 1, AM dose | 1432.6 Nanogram | Geometric Coefficient of Variation 30.6 |
| Placebo | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 7, AM dose | 3661.2 Nanogram | Geometric Coefficient of Variation 27.4 |
| Placebo | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 1, PM dose | 2080.2 Nanogram | Geometric Coefficient of Variation 29.5 |
| Placebo | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 7, PM dose | 3344.7 Nanogram | Geometric Coefficient of Variation 62 |
| GSK233705 50 µg Twice Daily | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 7, PM dose | 7328.5 Nanogram | Geometric Coefficient of Variation 36.6 |
| GSK233705 50 µg Twice Daily | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 1, AM dose | 3977.1 Nanogram | Geometric Coefficient of Variation 32.4 |
| GSK233705 50 µg Twice Daily | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 1, PM dose | 4913.3 Nanogram | Geometric Coefficient of Variation 39 |
| GSK233705 50 µg Twice Daily | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Ae, Day 7, AM dose | 6538.3 Nanogram | Geometric Coefficient of Variation 66.5 |
90% CI: [2.033, 3.213]
90% CI: [1.29, 2.095]
Secondary
Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe)
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose.
Time frame: Day 1 and 7 throughout 24 hours
Population: PK population was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 1, PM dose | 4.3 Percentage of dose | Standard Deviation 1.14 |
| Placebo | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 1, AM dose | 3.0 Percentage of dose | Standard Deviation 0.84 |
| Placebo | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 7, PM dose | 7.5 Percentage of dose | Standard Deviation 3.15 |
| Placebo | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 7, AM dose | 7.5 Percentage of dose | Standard Deviation 1.88 |
| GSK233705 50 µg Twice Daily | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 7, PM dose | 7.7 Percentage of dose | Standard Deviation 2.66 |
| GSK233705 50 µg Twice Daily | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 7, AM dose | 7.5 Percentage of dose | Standard Deviation 3.67 |
| GSK233705 50 µg Twice Daily | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 1, AM dose | 4.2 Percentage of dose | Standard Deviation 1.3 |
| GSK233705 50 µg Twice Daily | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Day 1, PM dose | 5.2 Percentage of dose | Standard Deviation 1.48 |
Secondary
Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr)
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study. 12 hour pharmacokinetic sampling was before evening dose.
Time frame: Day 1 and 7 throughout 24 hours
Population: PK population was used. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) | Day 1 | 36.2 Liters per hour | Geometric Coefficient of Variation 24.5 |
| Placebo | Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) | Day 7 | 19.4 Liters per hour | Geometric Coefficient of Variation 49.1 |
| GSK233705 50 µg Twice Daily | Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) | Day 7 | 15.2 Liters per hour | Geometric Coefficient of Variation 68.4 |
| GSK233705 50 µg Twice Daily | Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) | Day 1 | 27.5 Liters per hour | Geometric Coefficient of Variation 50.2 |
Secondary
Plasma Concentrations of GSK233705
Blood samples were collected at indicated time points. 12 hour pharmacokinetic (PK) sampling was before evening dose.
Time frame: Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose
Population: PK population was used; this was defined as all participants in the all subjects population for whom a PK sample was obtained and analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentrations of GSK233705 | Day 1, AM dose, pre-dose | NA Nanograms per milliliter | — |
| Placebo | Plasma Concentrations of GSK233705 | Day 1, AM dose, 5 minutes | 0.039 Nanograms per milliliter | Standard Deviation 0.0332 |
| Placebo | Plasma Concentrations of GSK233705 | Day 1, AM dose, 15 minutes | 0.028 Nanograms per milliliter | Standard Deviation 0.0128 |
| Placebo | Plasma Concentrations of GSK233705 | Day 1, PM dose, 5 minutes | 0.070 Nanograms per milliliter | Standard Deviation 0.0327 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, AM dose, 12 hour | NA Nanograms per milliliter | — |
| Placebo | Plasma Concentrations of GSK233705 | Day 1, AM dose, 1 hour | 0.012 Nanograms per milliliter | — |
| Placebo | Plasma Concentrations of GSK233705 | Day 1, AM dose, 6 hour | NA Nanograms per milliliter | — |
| Placebo | Plasma Concentrations of GSK233705 | Day 1, AM dose, 12 hour | NA Nanograms per milliliter | — |
| Placebo | Plasma Concentrations of GSK233705 | Day 1, PM dose, 30 minutes | 0.024 Nanograms per milliliter | Standard Deviation 0.0087 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, AM dose, pre-dose | 0.013 Nanograms per milliliter | Standard Deviation 0.0111 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, AM dose, 5 minutes | 0.062 Nanograms per milliliter | Standard Deviation 0.0513 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, AM dose, 15 minutes | 0.046 Nanograms per milliliter | Standard Deviation 0.0291 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, AM dose, 1 hour | 0.025 Nanograms per milliliter | Standard Deviation 0.0119 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, AM dose, 6 hour | 0.015 Nanograms per milliliter | Standard Deviation 0.0081 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, PM dose, 5 minutes | 0.068 Nanograms per milliliter | Standard Deviation 0.0477 |
| Placebo | Plasma Concentrations of GSK233705 | Day 7, PM dose, 30 minutes | 0.028 Nanograms per milliliter | Standard Deviation 0.0115 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, PM dose, 5 minutes | 0.218 Nanograms per milliliter | Standard Deviation 0.1091 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, AM dose, pre-dose | NA Nanograms per milliliter | — |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, AM dose, 15 minutes | 0.146 Nanograms per milliliter | Standard Deviation 0.0724 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, AM dose, 5 minutes | 0.181 Nanograms per milliliter | Standard Deviation 0.0948 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, PM dose, 30 minutes | 0.062 Nanograms per milliliter | Standard Deviation 0.012 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, AM dose, 12 hour | NA Nanograms per milliliter | — |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, PM dose, 30 minutes | 0.064 Nanograms per milliliter | Standard Deviation 0.0233 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, PM dose, 5 minutes | 0.209 Nanograms per milliliter | Standard Deviation 0.1066 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, AM dose, 6 hour | 0.028 Nanograms per milliliter | Standard Deviation 0.0085 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, AM dose, pre-dose | 0.024 Nanograms per milliliter | Standard Deviation 0.007 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, AM dose, 12 hour | 0.028 Nanograms per milliliter | Standard Deviation 0.0242 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, AM dose, 15 minutes | 0.090 Nanograms per milliliter | Standard Deviation 0.0331 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, AM dose, 1 hour | 0.061 Nanograms per milliliter | Standard Deviation 0.021 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, AM dose, 1 hour | 0.034 Nanograms per milliliter | Standard Deviation 0.0115 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 7, AM dose, 5 minutes | 0.226 Nanograms per milliliter | Standard Deviation 0.1257 |
| GSK233705 50 µg Twice Daily | Plasma Concentrations of GSK233705 | Day 1, AM dose, 6 hour | NA Nanograms per milliliter | — |
Secondary
Urine Concentrations of GSK233705
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data is presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose.
Time frame: Day 1 and 7 throughout 24 hours
Population: PK population was used.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Urine Concentrations of GSK233705 | Day 1, 0-12 hours | 124.6721 Nanograms per liter | Standard Deviation 35.34371 |
| Placebo | Urine Concentrations of GSK233705 | Day 1, 12-24 hours | 179.4939 Nanograms per liter | Standard Deviation 47.34615 |
| Placebo | Urine Concentrations of GSK233705 | Day 7, 0-12 hours | 316.6091 Nanograms per liter | Standard Deviation 80.41509 |
| Placebo | Urine Concentrations of GSK233705 | Day 7, 12-24 hours | 311.6291 Nanograms per liter | Standard Deviation 131.1778 |
| GSK233705 50 µg Twice Daily | Urine Concentrations of GSK233705 | Day 7, 12-24 hours | 643.1492 Nanograms per liter | Standard Deviation 218.4276 |
| GSK233705 50 µg Twice Daily | Urine Concentrations of GSK233705 | Day 1, 0-12 hours | 348.9206 Nanograms per liter | Standard Deviation 110.1697 |
| GSK233705 50 µg Twice Daily | Urine Concentrations of GSK233705 | Day 7, 0-12 hours | 629.6146 Nanograms per liter | Standard Deviation 311.2823 |
| GSK233705 50 µg Twice Daily | Urine Concentrations of GSK233705 | Day 1, 12-24 hours | 431.8806 Nanograms per liter | Standard Deviation 122.7514 |